Hematoporphyrin and some of its derivatives (HpD) have the tendency to be retained at higher concentrations in tumor tissues, and upon exposure to light generate singlet oxygen which destroys HpD containing tumor cells. The objective of this project is to exploit these properties for the development of a new modality of therapy for transitional cell carcinoma of the bladder (TCC). Preclinical and clinical studies will be carried out to develop the methodology and instrumentation and to evaluate the efficacy for their application. The specific aims of this research are: 1. To evaluate the specificity of retention of HpD by TCC: Studies will be carried out in animal models, cultured tumor cells and patients with TCC to access the specificity of HpD retention by TCC vs. non-tumor, inflammed or traumatized tissues of the bladder. 2. To explore the possibility of administering HpD by intravesical instillation. This will provide a direct, safer, and more effective means of HpD administration. 3. To study the photobiology of the bladder for defining the proper conditions for the photoradiation of bladder with HpD: In vitro and in vivo studies will be carried out to define the optimal wavelength and dosage of light for photoradiation in order to achieve maximum tumor killing with the minmum damage to non-tumor cells. This will enable us to predetermine the proper light dosage and wavelength for the photoradiation of different types and size of tumors, thus providing some assurance for a predictable response to the treatment. 4. To cary out trials in patients to evaluate the effectiveness and possible side effects of HpD phototherapy for TCC. 5. To develop a low cost convenient and effective instrument for the HpD photoradiation of bladder tumors. We believe that photoradiation therapy with HpD will be a powerful tool for the treatment of TCC of the bladder, especially those of low grade tumors (superficial or TIS). This project, therefore, has the potential of providing a new, effective, safe, and inexpensive means of treatment for otherwise uncontrollable low stage TCC of the bladder.